Influence of dissolved oxygen and shear conditions on clavulanic acid production by Streptomyces clavuligerus
Abstract
Clavulanic acid (CA), a potent beta-lactamase inhibitor, is produced by a filamentous bacterium. Here, the effect of DO and shear, expressed as impeller tip velocity, on CA production was examined. Cultivations were performed in a 4 L fermentor with speeds of 600, 800 and 1,000 rpm and a fixed air flow rate (0.5 vvm). Also, cultivation with automatic control of dissolved oxygen, at 50% air saturation, by varying stirrer speed and using a mixture of air and O(2) (10% v/v) in the inlet gas, and a cultivation with fixed stirrer speed of 800 rpm and air flow rate of 0.5 vvm, enriched with 10% v/v O(2), were performed. Significant variations in CA titer, CA production rate and O(2) uptake-rate were observed. It was also found that the DO level has no remarkable effect on CA production once a critical level is surpassed. The most significant improvement in CA production was related to high stirrer speeds.
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A pH of 6.8 is favorable for obtaining high titers of CA in submerged cultures.
“Previous studies have shown that CA stability increases at slightly acidic pH values [10,11]; several authors found a pH of 6.8 as favorable for obtaining high titers of CA in submerged cultures [5,7,9,12,13,14,15,16].”
From Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures (2019) · cites this paper as [12]
Rosa et al. (2005) showed that agitation speed has a positive correlation with clavulanic acid production.
“Another study showed that agitation speed has a positive correlation with clavulanic acid production (Rosa et al., 2005).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Rosa et al., 2005
Breakage and/or damage of bacterial cells upon exposure to such stress encourages neighboring cells to produce secondary metabolites in an attempt to survive and protect against the challenge.
“The breakage and/or damage of bacterial cells upon exposure to such stress in turn, encourage the neighboring cells to produce secondary metabolites in an attempt to survive and protect against the challenge (Toma et al., 1991; Joshi et al., 1996; Rosa et al., 2005).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Rosa et al., 2005
High speed stirring prevents cell clumping and causes cell shearing.
“It is believed that the high speed stirring prevents cell clumping and also causes cell shearing (Toma et al., 1991; Rosa et al., 2005).”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Rosa et al., 2005
Rosa et al. (2005) showed that high speed stirring promoted clavulanic acid production, which was associated with a lower amount of biomass production.
“Rosa et al. (2005) showed that the high speed stirring promoted the production of clavulanic acid, which was associated with a lower amount of biomass production.”
From Fermentation Conditions that Affect Clavulanic Acid Production in Streptomyces clavuligerus: A Systematic Review (2016) · cites this paper as Rosa et al. (2005)
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Ser, H.-L., Law, J. W.-F., Chaiyakunapruk, N., Jacob, S. A., Palanisamy, U. D., Chan, K.-G., Goh, B.-H., & Lee, L.-H. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00522 · Cited by 90 · see citing works
“Rosa et al. (2005) showed that the high speed stirring promoted the production of clavulanic acid, which was associated with a lower amount of biomass production.”
BackgroundInfluentialDegradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures
Gómez-Ríos, D., Ramírez-Malule, H., Neubauer, P., Junne, S., & Ríos-Estepa, R. (2019) · Antibiotics · doi:10.3390/antibiotics8010006 · Cited by 17 · see citing works
- Authors
- Rosa, J. C., Neto, A. B., Hokka, C. O., & Badino, A. C.
- Affiliations
- Universidade Federal de São Carlos (BR)
- Venue
- Bioprocess and Biosystems Engineering
- Published
- 2004-12-09
- Volume
- 27
- Issue
- 2
- Pages
- 99-104
- ISSN
- 1615-7591 (ISSN-L)
- 1615-7605
- OpenAlex
- W2066509362
- Cited by
- 68
- References
- 0
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 3 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 7 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 6
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Bioprocess and Biosystems Engineering (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Fluid Dynamics and Mixing
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Enzyme Production and Characterization
- Keywords
- clavulanic acid, Streptomyces clavuligerus, dissolved oxygen, shear stress, oxygen uptake rate, oxygen enrichment, aeration, beta-lactamase inhibitors, fermentation optimization
- MeSH terms
- Culture Media, Glycerol, Oxygen, Rheology, Solubility, Streptomyces, Cell Culture Techniques, Bioreactors, Clavulanic Acid, Shear Strength, Mechanotransduction, Cellular
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